Pleiotropic effects of a disrupted K+ channel gene: reduced body weight, impaired motor skill and muscle contraction, but no seizures.
To investigate the roles of K+ channels in the regulation and fine-tuning of cellular excitability, we generated a mutant mouse carrying a disrupted gene for the fast activating, voltage-gated K+ channel Kv3.1. Kv3.1-/- mice are viable and fertile but have significantly reduced body weights compared with their Kv3.1+/- littermates. Wild-type, heterozygous, and homozygous Kv3.1 channel-deficient mice exhibit similar spontaneous locomotor and exploratory activity. In a test for coordinated motor skill, however, homozygous Kv3.1-/- mice perform significantly worse than their heterozygous Kv3.1+/- or wild-type littermates. Both fast and slow skeletal muscles of Kv3.1-/- mice are slower to reach peak force and to relax after contraction, consequently leading to tetanic responses at lower stimulation frequencies. Both mutant muscles generate significantly smaller contractile forces during a single twitch and during tetanic conditions. Although Kv3.1-/- mutants exhibit a normal auditory frequency range, they show significant differences in their acoustic startle responses. Contrary to expectation, homozygous Kv3.1-/- mice do not have increased spontaneous seizure activity.


Estimated Lifetime Medical and Work-Loss Costs of Fatal Injuries--United States, 2013.
Injury-associated deaths have substantial economic consequences. In 2013, unintentional injury was the fourth leading cause of death, suicide was the tenth, and homicide was the sixteenth; these three causes accounted for approximately 187,000 deaths in the United States. To assess the economic impact of fatal injuries, CDC analyzed death data from the National Vital Statistics System for 2013, along with cost of injury data using the Web-Based Injury Statistics Query and Reporting System. This report updates a previous study that analyzed death data from the year 2000, and employs recently revised methodology for determining the costs of injury outcomes, which uses the most current economic data and incorporates improvements for estimating medical costs associated with injury. Number of deaths, crude and age-specific death rates, and total lifetime work-loss costs and medical costs were calculated for fatal injuries by sex, age group, intent (intentional versus unintentional), and mechanism of injury. During 2013, the rate of fatal injury was 61.0 per 100,000 population, with combined medical and work-loss costs exceeding $214 billion. Costs from fatal injuries represent approximately one third of the total $671 billion medical and work-loss costs associated with all injuries in 2013. The magnitude of the economic burden associated with injury-associated deaths underscores the need for effective prevention.


[Hygiene practices in a street market in the city of Salvador, Bahia State].
The main objective of this research is to understand the meaning of the practices concerning food hygiene in a street market in Salvador, the capital of Bahia State in Brazil. The ethnographic study presents two main categories for symbolic production related to hygiene practices: cleanliness as order and dirtiness as disorder. These cultural codes make correspondence with the studies of Mary Douglas and Nobert Elias. The codes present particularities to decode everyday life, in which concept and hygiene practices are aspects normalized, in daily activity, for persons who share the space of street market: vendors, consumers, street cleaners and official inspectors. The techno-scientific knowledge and sanitary legislation are strange to the symbolic system of street market vendors. The laws are ineffective and their influence is of little importance in the creation of hygiene practices. Official inspectors' attitudes are coercive and punitive and do not take into account any cultural values when enforcing new hygiene practices.


Measuring the anticoagulant effect of low molecular weight heparins in the critically ill.
Antithrombotic prophylaxis in critically ill patients frequently fails. Venous thromboembolism is associated with adverse clinical outcomes, including a prolonged intensive care unit stay and death. A potential mechanism by which critically ill patients may be predisposed to antithrombotic failure is the inability to achieve 'prophylactic' anticoagulant drug levels as a result of impaired absorption. For example, previous studies have shown that patients on inotropes have reduced serum levels of low molecular weight heparin, presumably on the basis of reduced absorption from the subcutaneous injection site. In the previous issue of the journal, Rommers and colleagues examined whether subcutaneous edema reduces absorption of a low molecular weight heparin; although small, and thus underpowered, the authors failed to find any relationship between the level of low molecular weight heparin and the presence of edema. These findings provide reassurance that subcutaneously administered medications may be used in critically ill patients with edema.


Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer.
Understanding competing risks for mortality is critical in determining prognosis among men with non-metastatic castration-resistant prostate cancer (nmCRPC), a disease state that often affects older men and has substantial heterogeneity in risk of cancer mortality. We sought to determine the impact of age, comorbidity, and PSA doubling time (PSADT) on competing risks for mortality in men with nmCRPC. We conducted a retrospective analysis of 1238 patients diagnosed with nmCRPC in 2000-2015 in the SEARCH database. Multivariable Cox proportional hazards and competing risks regression were used to determine the hazards of overall, prostate cancer-specific (PCSM), and other-cause mortality (OCM) across age, Charlson comorbidity index (CCI), and PSADT subgroups. Men with nmCRPC were elderly (median age 77) and had substantial comorbidity burdens (CCI > 1 n = 701, 57%). Multivariable Cox analysis showed higher CCI was associated with higher hazard of OCM, while slower PSADT was associated with lower hazard of PCSM across all age subgroups. Among those with CCI ≥ 3 (vs. CCI0), the hazard ratio of OCM was 2.7 (95% CI 1.1-6.3), 2.0 (95% CI 1.1-3.6), and 2.5 (95% CI 1.5-4.0) for those aged <70, 70-79, and ≥80, respectively. Among those with PSADT ≥ 9 months (vs. < 9 months), the hazard ratios for PCSM were 0.5 (95% CI 0.3-0.9), 0.6 (95% CI 0.4-0.9), and 0.6 (95% CI 0.4-0.9) for those aged <70, 70-79, and ≥80. Competing risks curves revealed PCSM was the predominant cause of death for those with PSADT < 9 months across all age and comorbidity groups. PCSM and OCM were relatively equal competitors for mortality among those with PSADT≥9 months except those aged > 80 with CCI ≥ 3, in whom OCM was the predominant cause of death. Among men with nmCRPC, age, comorbidity, and PSADT are associated with risk and cause of death and may assist clinicians in counseling patients regarding cancer prognosis.


Expression of the MRP gene-encoded conjugate export pump in liver and its selective absence from the canalicular membrane in transport-deficient mutant hepatocytes.
We have previously shown that the multi-drug resistance protein (MRP) mediates the ATP-dependent membrane transport of glutathione S-conjugates and additional amphiphilic organic anions. In the present study we demonstrate the expression of MRP in hepatocytes where it functions in hepatobiliary excretion. Analysis by reverse transcription-PCR of human and normal rat liver mRNA resulted in two expected cDNA fragments of MRP. Four different antibodies against MRP reacted on immunoblots with the glycoprotein of about 190 kD from human canalicular as well as basolateral hepatocyte membrane preparations. A polyclonal antibody directed against the carboxy-terminal sequence of MRP detected the rat homolog of MRP in liver. Double immunofluorescence microscopy and confocal laser scanning microscopy showed the presence of human MRP and rat Mrp in the canalicular as well as in the lateral membrane domains of hepatocytes. The transport function of the mrp gene-encoded conjugate export pump was assayed in plasma membrane vesicles with leukotriene C4 as a high-affinity glutathione S-conjugate substrate. The deficient ATP-dependent conjugate transport in canalicular membranes from TR- mutant rat hepatocytes was associated with a lack of amplification of one of the mrp cDNA fragments and with a selective loss of Mrp on immunoblots of canalicular membranes. Double immunofluorescence microscopy of livers from transport-deficient TR- mutant rats localized Mrp only to the lateral but not to the canalicular membrane. Our results indicate that the absence of Mrp or an isoform of Mrp from the canalicular membrane is the basis for the hereditary defect of the hepatobiliary excretion of anionic conjugates by the transport-deficient hepatocyte.


Anthocyanin-enriched bilberry and blackcurrant extracts modulate amyloid precursor protein processing and alleviate behavioral abnormalities in the APP/PS1 mouse model of Alzheimer's disease.
A growing body of epidemiological evidence suggests that fruit and vegetable juices containing various phenolic compounds can reduce the risk of Alzheimer's disease (AD). As the altered amyloid precursor protein (APP) processing leading to increased β-amyloid (Aβ) production is a key pathogenic feature of AD, we elucidated the effects of different polyphenols on neuroprotection and APP processing under different in vitro stress conditions. The effects of these compounds were also investigated in transgenic AD mice (APdE9). Free radical toxicity and apoptosis were induced in human SH-SY5Y neuroblastoma cells overexpressing APP751. Menadione-induced production of reactive oxygen species was significantly decreased upon treatment with myricetin, quercetin or anthocyanin-rich extracts in a dose-dependent manner. However, these extracts did not affect caspase-3 activation, APP processing or Aβ levels upon staurosporine-induced apoptosis. APdE9 mice fed with anthocyanin-rich bilberry or blackcurrant extracts showed decreased APP C-terminal fragment levels in the cerebral cortex as compared to APdE9 mice on the control diet. Soluble Aβ40 and Aβ42 levels were significantly decreased in bilberry-fed mice as compared to blackcurrant-fed mice. Conversely, the ratio of insoluble Aβ42/40 was significantly decreased in blackcurrant-fed mice relative to bilberry-fed mice. Both berry diets alleviated the spatial working memory deficit of aged APdE9 mice as compared to mice on the control diet. There were no changes in the expression or phosphorylation status of tau in APdE9 mice with respect to diet. These data suggest that anthocyanin-rich bilberry and blackcurrant diets favorably modulate APP processing and alleviate behavioral abnormalities in a mouse model of AD.


Calcium transport in the rabbit superficial proximal convoluted tubule.
Calcium transport was studied in isolated S2 segments of rabbit superficial proximal convoluted tubules. 45Ca was added to the perfusate for measurement of lumen-to-bath flux (JlbCa), to the bath for bath-to-lumen flux (JblCa), and to both perfusate and bath for net flux (JnetCa). In these studies, the perfusate consisted of an equilibrium solution that was designed to minimize water flux or electrochemical potential differences (PD). Under these conditions, JlbCa (9.1 +/- 1.0 peq/mm X min) was not different from JblCa (7.3 +/- 1.3 peq/mm X min), and JnetCa was not different from zero, which suggests that calcium transport in the superficial proximal convoluted tubule is due primarily to passive transport. The efflux coefficient was 9.5 +/- 1.2 X 10(-5) cm/s, which was not significantly different from the influx coefficient, 7.0 +/- 1.3 X 10(-5) cm/s. When the PD was made positive or negative with use of different perfusates, net calcium absorption or secretion was demonstrated, respectively, which supports a major role for passive transport. These results indicate that in the superficial proximal convoluted tubule of the rabbit, passive driving forces are the major determinants of calcium transport.


Hepatoprotective effect of stem of Musa sapientum Linn in rats intoxicated with carbon tetrachloride.
The study was designed to evaluate the hepatoprotective activity of aqueous extract of central stem of Musa sapientum (AqMS) against carbon tetrachloride induced hepatotoxicity in rats. Animals were divided into six groups. Group I served as normal control. Group II, III, IV, V & VI were administered CCl(4) mixed with olive oil 1:1 (1.5 mL/kg) I.P., twice a week for 5 weeks. Group II was maintained as CCl(4) intoxicated control. Group III, IV and V received AqMS at a dose of 25, 50 and 100 mg/kg. Group VI received silymarin 100 mg/kg for 5 weeks orally once daily. Marker enzymes of hepatic functions estimated in serum were AST, ALT and ALP. Antioxidant parameters estimated were MDA and GSH in blood and liver and SOD in blood, after fifth week, animals were sacrificed, livers dissected out and evaluated for histomorphological changes. There was significant rise in AST, ALT and ALP in CCl(4) intoxicated control group II. Treatment with AqMS prevented rise in levels of these enzymes. There was significant rise in MDA and fall in GSH in blood and liver in group II, indicating increased lipid peroxidation and oxidative stress upon CCl(4) administration. Treatment with AqMS prevented rise in MDA & increased GSH in treated group. SOD levels were decreased in group II while groups treated with AqMS showed significant rise (p < 0.05). Maximum hepatoprotective effect was observed with 50 mg/kg dose. Hepatoprotective effect observed with this dose was comparable to standard hepatoprotective drug silymarin. The results of pathological study also support the results of biochemical findings. the results of the present study indicate that stem of Musa sapientum possess hepatoprotective effect and probably it is due to it's antioxidant property.


Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice.
To develop recommendations on monitoring for adverse events (AEs) of low-dose glucocorticoid (GC) therapy (≤7.5 mg prednisone or equivalent daily) in clinical trials and daily practice. Literature was searched for articles containing information on incidence and monitoring of GC-related AEs using PubMed, EMBASE and Cochrane databases. Second, the authors searched for broad accepted guidelines on the monitoring of certain AEs (eg, WHO guidelines on screening for diabetes). Available data were summarised and discussed among experts (rheumatologists and patients) of the EULAR Task Force to decide which potential AEs should be monitored, how and at which interval. Data on monitoring proved to be scarce; most articles were focused on therapeutic effects of GCs, not on occurrence and monitoring of AEs. Most recommendations had to be based on consensus. Those for clinical trials aimed at getting insights into incidence, prevalence and clinical relevance of AEs to create a comprehensive and valid AE-profile of GC therapy. The set of AEs to monitor is therefore more extensive, and often consists of assessments at baseline and at end of trials. Recommendations for daily practice are meant to protect patients from real dangers, which can be prevented or treated. Standard care monitoring needs NOT be extended for patients on low-dose GC therapy, except for osteoporosis (follow national guidelines), and baseline assessments of ankle edema, fasting blood glucose and risk factors for glaucoma. Given the incompleteness of literature data, consensus-based recommendations on monitoring for GC-related AEs were created, separately for daily practice and clinical trials.


Basic fibroblast growth factor confers a less malignant phenotype in MDA-MB-231 human breast cancer cells.
Basic fibroblast growth factor (FGF-2) expression is associated with a more differentiated phenotype, earlier stage of disease, and a better prognosis in breast cancer patients. To determine whether expression of FGF-2 can cause a less malignant phenotype, we engineered MDA-MB-231 cells, a highly dedifferentiated, invasive breast cancer cell line, to express different isoforms of FGF-2. Cells expressed either cytoplasmic, nuclear, or a combination of both FGF-2 isoforms. Western blots of 2 M NaCl washes and of conditioned medium demonstrated that these cells did not export FGF-2. Cells expressing FGF-2 had levels of fibroblast growth factor receptors equivalent with those of control cells. Transformation was assayed by anchorage-independent colony formation and tumor formation in athymic mice. All of the constructs expressing various FGF-2 isoforms had a 60-70% reduction in colony formation in soft agar, but only cells expressing the Mr 18,000 FGF-2 isoform formed fewer and smaller tumors in mice. To determine potential mechanisms responsible for a less malignant phenotype, experiments measuring invasion in Matrigel, the secretion of matrix metalloprotease activity and migration in a modified Boyden chamber and in a patch wound motility assay were carried out. Cells expressing the Mr 18,000 cytoplasmic FGF-2 moiety had a 45% decrease in invasion in Matrigel compared to vector-transfected controls. Cells expressing Mr 18,000 FGF-2 had an increase in Mr 97,000 and Mr 48,000 collagenase, demonstrating that the decreased invasive potential was not due to a down-regulation of gelatinolytic or caseinolytic matrix metalloproteinases. However, motility was decreased in both assays, primarily in cells expressing Mr 18,000 FGF-2, whereas exogenous recombinant human FGF-2 had no effect. These studies demonstrate for the first time that FGF-2 expression can cause a less malignant phenotype in breast cancer cells, possibly as a result of decreased motility and invasion.


Computers in science and technology: early indications.
Over the past 20 years computer technology has advanced rapidly, especially in the areas of logic and memory. Continued growth at a similar pace can be expected through and probably beyond the 1980's. The technology has already had such major effects on scientific research and engineering that it is of practical importance to try to predict its evolution and uses. It is likely that the trend toward smaller, faster, and cheaper circuits made possible by improved lithographic techniques will continue, resulting in a factor of 10 increase in speed of central processing units and an even greater increase in speed of single-chip microprocessors by the end of the decade. Similar progress is expected in the areas of memory, magnetic storage, printers, and displays. Overall, approximately 20 percent growth annually in the capability of computing systems can be projected. How this continually increasing computing power will affect scientific and engineering activity is more difficult to predict, but some patterns are emerging. Observations of technical personnel at the IBM research laboratory at Yorktown, New York, where the average user has access to a large amount of computing capability and to a worldwide computer network, indicate that workers in different areas have reacted to computer technology in different ways. Whereas engineers have used computing power, displays, and the ability to communicate or share information more or less equally, management has used communication most and scientists have put the greatest value on computing power and displays.


Review of psittacine beak and feather disease and its effect on Australian endangered species.
Since it was first described in the early 1980s, psittacine beak and feather disease (PBFD) has become recognised as the dominant viral pathogen of psittacine birds in Australia. Our aim was to evaluate and review the effect of PBFD and its position as a key threatening process to Australian psittacine bird species. We review the origin/evolutionary pathways and potential threat of PBFD to endangered psittacine bird populations and captive-breeding flocks. The most recent beak and feather disease virus (BFDV) phylogenetic analyses indicate that all endangered Australian psittacine bird species are susceptible to, and equally likely to be infected by, BFDV genotypes from a range of host psittacine species. Management of the disease in captive-breeding programs has relied on testing and culling, which has proven costly. The risk of PBFD should be considered very carefully by management teams contemplating the establishment of captive-breeding flocks for endangered species. Alternative disease prevention tools, including vaccination, which are increasingly being used in wildlife health, should be considered more seriously for managing and preventing PBFD in captive flocks of critically endangered species.


Assessment of Workplace Stigma and Discrimination among People Living with HIV/AIDS Attending Antiretroviral Clinics in Health Institutions in Enugu, Southeast Nigeria.
The onset of HIV/AIDS has increased stigma and discrimination at workplaces, making those with these ailments worried about going to work to avoid being victimized. Most previous works focussed on stigma and discrimination in the communities with little emphasis on what occurs in the workplaces. This study assessed the prevalence of workplace stigma and discrimination among people living with HIV/AIDS (PLWHA) attending antiretroviral (ARV) clinics in health institutions in Enugu, southeast Nigeria. A cross-sectional descriptive study was done between February and May of 2014 using a selfadministered questionnaire to assess 489 PLWHA attending ARV clinics. Out of 489 studied, 255 (52.1%) were females. About 23.7% said being HIV positive had affected their relationship with other workers and 20.7% were blamed for their condition. Some were not given time off to go to hospital (72.5%). The commonest fears of PLWHA were stigmatization/discrimination from other workers (78.1%) and dying from the disease (62.8%). Gender did not significantly affect the way PLWHA were stigmatized or discriminated against in their workplaces. However, those who were employed in private establishments were more likely to have their schedule changed due to their status compared to government employees (p < 0.01). Other discriminating practices were not significantly different between government and private employees. The prevalence of stigma and discrimination in workplaces is high. Efforts should be made by agencies to reduce such social problems in the workplace since they can affect overall management and productivity.


Increases in bioactive lipids accompany early metabolic changes associated with β-cell expansion in response to short-term high-fat diet.
Pancreatic β-cell expansion is a highly regulated metabolic adaptation to increased somatic demands, including obesity and pregnancy; adult β cells otherwise rarely proliferate. We previously showed that high-fat diet (HFD) feeding induces mouse β-cell proliferation in less than 1 wk in the absence of insulin resistance. Here we metabolically profiled tissues from a short-term HFD β-cell expansion mouse model to identify pathways and metabolite changes associated with β-cell proliferation. Mice fed HFD vs. chow diet (CD) showed a 14.3% increase in body weight after 7 days; β-cell proliferation increased 1.75-fold without insulin resistance. Plasma from 1-wk HFD-fed mice induced β-cell proliferation ex vivo. The plasma, as well as liver, skeletal muscle, and bone, were assessed by LC and GC mass-spectrometry for global metabolite changes. Of the 1,283 metabolites detected, 159 showed significant changes [false discovery rate (FDR) < 0.1]. The majority of changes were in liver and muscle. Pathway enrichment analysis revealed key metabolic changes in steroid synthesis and lipid metabolism, including free fatty acids and other bioactive lipids. Other important enrichments included changes in the citric acid cycle and 1-carbon metabolism pathways implicated in DNA methylation. Although the minority of changes were observed in bone and plasma (<20), increased p-cresol sulfate was increased >4 fold in plasma (the largest increase in all tissues), and pantothenate (vitamin B5) decreased >2-fold. The results suggest that HFD-mediated β-cell expansion is associated with complex, global metabolite changes. The finding could be a significant insight into Type 2 diabetes pathogenesis and potential novel drug targets.


An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage.
When trying to conceive 1% of couples have recurrent miscarriages, defined as three or more consecutive pregnancy losses. This is not accounted for by the known incidence of chromosomal aneuploidy in miscarriage, and it has been suggested that there is an immunological aetiology. The endometrial mucosa is populated by a variety of immune cells which in addition to providing host pathogen immunity must facilitate pregnancy. Here we characterise the endometrial CD8-T cell population during the embryonic window of implantation and find that the majority of cells are tissue resident memory T cells with high levels of CD69 and CD103 expression, proteins that prevent cells egress. We demonstrate that unexplained recurrent miscarriage is associated with significantly decreased expression of the T-cell co-receptor CD8 and tissue residency marker CD69. These cells differ from those found in control women, with less expression of CD127 indicating a lack of homeostatic cell control through IL-7 signalling. Nevertheless this population is resident in the endometrium of women who have RM, more than three months after the last miscarriage, indicating that the memory CD8-T cell population is altered in RM patients. This is the first evidence of a differing pre-pregnancy phenotype in endometrial immune cells in RM.


Endothelial cell autoantibodies in predicting declining renal function, end-stage renal disease, or death in adult type 2 diabetic nephropathy.
Albuminuria is a strong predictor of diabetic nephropathy chronic kidney disease outcomes. Yet, therapeutic albuminuria-lowering has not consistently translated into a reduction in clinical events suggesting the involvement of additional pathogenic factors. Our hypothesis is that anti-endothelial cell autoantibodies play a role in development and progression in diabetic nephropathy. We determined anti-endothelial cell antibody (AECA) bioactivity in protein A-elutes of baseline plasma in 305 participants in the VA NEPHRON-D study, a randomized trial of angiotensin receptor blocker (ARB) or dual ARB plus angiotensin-converting enzyme inhibitor therapy in type 2 diabetes with proteinuric nephropathy. Thirty-eight percent (117/305) of participants had significantly reduced endothelial cell survival ( ≤80%) in the IgG fraction of plasma. A VA NEPHRON-D primary endpoint [end-stage renal disease (ESRD), significant reduction in estimated glomerular filtration rate, or death] was experienced by 58 individuals. In adjusted Cox regression analysis, there was a significant interaction effect of baseline anti-endothelial cell-mediated cell survival and albuminuria on the hazard rate (HR) for primary composite endpoint (P = 0.017). Participants lacking strongly inhibitory antibodies with albuminuria ≥1 g/g creatinine had a significantly increased primary event hazard ratio, 3.41 - 95% confidence intervals (CI 1.84-6.33; P < 0.001) compared to those lacking strongly inhibitory antibodies with lower baseline albuminuria ( <1 g/g creatinine). These results suggest that anti-endothelial cell antibodies interact significantly with albuminuria in predicting the composite endpoint of death, ESRD, or substantial decline in renal function in older, adult type 2 diabetic nephropathy.


Irish Medical Students Understanding of the Intern Year.
Upon completion of medical school in Ireland, graduates must make the transition to becoming interns. The transition into the intern year may be described as challenging as graduates assume clinical responsibilities. Historically, a survey of interns in 1996 found that 91% felt unprepared for their role. However, recent surveys in 2012 have demonstrated that this is changing with preparedness rates reaching 52%. This can be partially explained by multiple initiatives at the local and national level. Our study aimed evaluate medical student understanding of the intern year and associated factors. An online, cross-sectional survey was sent out to all Irish medical students in 2013 and included questions regarding their understanding of the intern year. Two thousand, two hundred and forty-eight students responded, with 1,224 (55.4%) of students agreeing or strongly agreeing that they had a good understanding of what the intern year entails. This rose to 485 (73.7%) among senior medical students. Of junior medical students, 260 (42.8%) indicated they understood what the intern year, compared to 479 (48.7%) of intermediate medical students. Initiatives to continue improving preparedness for the intern year are essential in ensuring a smooth and less stressful transition into the medical workforce.


A microtubule-associated protein from Xenopus eggs that specifically promotes assembly at the plus-end.
We have isolated a protein factor from Xenopus eggs that promotes microtubule assembly in vitro. Assembly promotion was associated with a 215-kD protein after a 1,000-3,000-fold enrichment of activity. The 215-kD protein, termed Xenopus microtubule assembly protein (XMAP), binds to microtubules with a stoichiometry of 0.06 mol/mol tubulin dimer. XMAP is immunologically distinct from the Xenopus homologues to mammalian brain microtubule-associated proteins; however, protein species immunologically related to XMAP with different molecular masses are found in Xenopus neuronal tissues and testis. XMAP is unusual in that it specifically promotes microtubule assembly at the plus-end. At a molar ratio of 0.01 mol XMAP/mol tubulin the assembly rate of the microtubule plus-end is accelerated 8-fold while the assembly rate of the minus-end is increased only 1.8-fold. Under these conditions XMAP promotes a 10-fold increase in the on-rate constant (from 1.4 s-1.microM-1 for microtubules assembled from pure tubulin to 15 s-1.microM-1), and a 10-fold decrease in off-rate constant (from 340 to 34 s-1). Given its stoichiometry in vivo, XMAP must be the major microtubule assembly factor in the Xenopus egg. XMAP is phosphorylated during M-phase of both meiotic and mitotic cycles, suggesting that its activity may be regulated during the cell cycle.


Tubulointerstitial nephritis and uveitis syndrome.
Tubulointerstitial nephritis and uveitis syndrome (TINU) is a specific form of intraocular inflammation (uveitis) combined with kidney disease that was first described in two patients by Dobrin et al. in 1975. Since then, approximately 200 more cases have been published. The cause of the disease is still unknown. A hypersensitivity reaction is suspected, especially an infection or very rarely a medication reaction is thought to trigger the disease. It is considered to be a rare disease and thus unfortunately is still unfamiliar to most ophthalmologists. Therefore, it is frequently overlooked in the differential diagnosis. In this review we want to show advances in diagnostics and treatment as well as progress in deciphering the pathogenesis. Beta-2 microglobulin (Ub2MG) analysis in urine and human leukocyte antigen (HLA) typing is helpful to diagnose TINU cases. A high association of HLA-DRB1*01 has been shown with TINU. A first single case report suggests a common antibody production against ocular and renal proteins. TINU is a common cause of uveitis among patients who present with bilateral, anterior uveitis of sudden onset. It is more frequent in children and apparently in boys. Although the activity of the eye disease can persist for many months, it is usually controlled with little treatment and the outcome is very good.


Impact of Symptoms of Maternal Anxiety and Depression on Quality of Life of Children with Cerebral Palsy.
Cerebral palsy (CP) interferes with the quality of life (QOL) of children with CP, and given that parents report having to often guide their children's decision making, it is important to understand the psychosocial factors that have a potential influence on parent-proxy reports. The purpose of this study was to investigate the impact of maternal anxiety and depression symptoms on parent proxy-reported health-related QOL (HRQOL) for children with CP, while controlling other clinical and demographical variables that may have affect HRQOL. The HRQOL scores of 97 outpatients with CP, aged 7-18 years, were assessed using the Pediatric QOL Inventory, Parent version (PedsQL-P). Each patient's type of CP, gross and fine motor function levels, severity of intellectual disability (ID), and other clinical variables were recorded. The levels of depression symptoms in each mother were assessed using the Beck Depression Inventory (BDI), and the levels of anxiety symptoms were assessed with the Beck Anxiety Inventory (BAI). According to regression analyses, male gender, severity of ID, and higher mothers' BAI scores had negative effects on the PedsQL-P physical scores, and severity of ID and higher mothers' BDI scores had negative effects on the PedsQL-P psychosocial scores. Regarding the determinants of total HRQOL, severity of ID, GMFCS score, and higher mothers' BDI scores negatively impacted the PedsQL-P total scores. Our findings show significant predictor effects of the mothers' anxiety and depressive symptoms, independent from other clinical variables, on the mother-rated HRQOL scores in children with CP.


Psychological treatments for the management of irritable bowel syndrome.
No consensus exists on the optimal treatment for irritable bowel syndrome (IBS). Psychological treatments are increasingly advocated but their effectiveness is unclear. To evaluate the efficacy of psychological interventions for the treatment of irritable bowel syndrome. A computer assisted search of MEDLINE, EMBASE, PsychInfo, CINAHL, Web of Science, The Cochrane Library and Google Scholar was performed for the years 1966-2008. Local databases were searched in Europe. Randomised trials comparing single psychological interventions with either usual care or mock interventions in patients over 16 years of age. No language criterion was applied. The search identified 25 studies that fulfilled the inclusion criteria. The relative risk (RR), risk difference (RD), number needed to treat (NNT) and standardized mean difference (SMD) along with 95% confidence intervals were calculated using a random effects model for each outcome. Psychological interventions as a group The SMD for symptom score improvement at 2 and 3 months was 0.97 (95% CI 0.29 to 1.65) and 0.62 (95% CI 0.45 to 0.79) respectively compared to usual care. Against placebo, the SMDs were 0.71 (95% CI 0.08 to 1.33) and -0.17 (95% CI -0.45 to 0.11) respectively. For improvement of abdominal pain, the SMDs at 2 and 3 months were 0.54 (95%CI 0.10 to 0.98) and 0.26 (95% CI 0.07 to 0.45) compared to usual care. The SMD from placebo at 3 months was 0.31 (95% CI -0.16 to 0.79). For improvement in quality of life, the SMD from usual care at 2 and 3 months was 0.47 (95%CI 0.11 to 0.84) and 0.31 (95%CI -0.16 to 0.77) respectively. Cognitive behavioural therapy The SMD for symptom score improvement at 2 and 3 months was 0.75 (95% CI -0.20 to 1.70) and 0.58 (95% CI 0.36 to 0.79) respectively compared to usual care. Against placebo, the SMDs were 0.68 (95% CI -0.01 to 1.36) and -0.17 (95% CI -0.45 to 0.11) respectively. For improvement of abdominal pain, the SMDs at 2 and 3 months were 0.45 (95% CI 0.00 to 0.91) and 0.22 (95% CI -0.04 to -0.49) compared to usual care. Against placebo the SMD at 3 months was 0.33 (95% CI -0.16 to 0.82). For improvement in quality of life, the SMDs at 2 and 3 months compared to usual care were 0.44 (95% CI 0.04 to 0.85) and 0.92 (95% CI 0.07 to 1.77) respectively.Interpersonal psychotherapy The RR for adequate relief of symptoms was 2.02 (95% CI 1.13 to 3.62), RD 0.30 (95% CI 0.13 to 0.46), NNT 4 for comparison with care as usual. The SMD for improvement of symptom score was 0.35 (95% CI -0.75 to 0.05) compared with usual care. Relaxation/Stress management The SMD in symptom score improvement at 2 months was 0.50 (95%CI 0.02 to 0.98) compared with usual care. The SMD in improvement of abdominal pain at 3 months was 0.02 (95%CI -0.56 to 0.61) compared with usual care. Long term results Very few long term follow-up results were available. There was no convincing evidence that treatment effects were sustained following completion of treatment for any treatment modality. Psychological interventions may be slightly superior to usual care or waiting list control conditions at the end of treatment although the clinical significance of this is debatable. Except for a single study, these therapies are not superior to placebo and the sustainability of their effect is questionable. The meta-analysis was significantly limited by issues of validity, heterogeneity, small sample size and outcome definition. Future research should adhere to current recommendations for IBS treatment trials and should focus on the long-term effects of treatment.


Exclusive breastfeeding among women taking HAART for PMTCT of HIV-1 in the Kisumu Breastfeeding Study.
One of the most effective ways to promote the prevention of mother-to-child transmission (PMTCT) of HIV-1 in resource-limited settings is to encourage HIV-positive mothers to practice exclusive breastfeeding (EBF) for the first 6 months post-partum while they receive antiretroviral therapy (ARV). Although EBF reduces mortality in this context, its practice has been low. We studied the rate of adherence to EBF and assessed associated maternal and infant characteristics using data from a phase II PMTCT clinical trial conducted in Western Kenya which included a counseling intervention to encourage EBF by all participants. We analyzed data from the Kisumu Breastfeeding Study (KiBS), conducted between July 2003 and February 2009. This study enrolled a total of 522 HIV-1 infected pregnant women. Data on breastfeeding were available for 480 mother-infant pairs. Infant feeding and general nutrition counseling began at 35 weeks gestation and continued throughout the 6 month post-partum intervention period, following World Health Organization (WHO) infant feeding guidelines. Data on infant feeding were collected during routine clinic visits and home visits using food frequency questionnaires and dietary recall methods. Participants were instructed to exclusively breastfeed until initiation of weaning at 5.5 months post-partum. We used Kaplan-Meier methods to estimate the rates of EBF at 5.25 months post-partum, stratified by maternal and infant characteristics measured at enrollment, delivery, and 2 weeks post-partum. The estimated EBF rate at 5.25 months post-partum was 80.4%. Only 3% of women introduced other foods (most commonly water with or without glucose, cow's milk, formula, and fruit) by 2 months; this percentage increased to 5% of women by 4 months. Women who had ≥3 previous births (p < 0.01) and who were not living with the infant's father (p = 0.04) were more likely to exclusively breastfeed. Mixed feeding was more common for male infants than for female infants (p = 0.04). Exclusive breastfeeding was common in this clinical trial, which emphasized EBF as a best practice until infants reached 5.5 months of age. Counseling initiated prior to delivery and continued during the post-partum period provided a consistent message reinforcing the benefits of EBF. The findings from this study suggest high adherence to EBF in resource limited settings can be achieved by a comprehensive counseling intervention that encourages EBF.


Anti-cytokines and cytokines in the treatment of rheumatoid arthritis.
The treatment approach to rheumatoid arthritis has undergone a major evolutionary change in recent years in part as a consequence of growing appreciation of the severity of this condition and in part due to very considerable progress in understanding the important role of cytokines in the immunopathogenesis of this disease. The major focus of this review is on the rationale for targeting TNFalpha and IL-1 in rheumatoid arthritis and the results of clinical studies designed to assess the validity of this therapeutic approach. Recently published studies confirm that the long term use of a several biological agents targeting TNFalpha give rise to sustained improvements in symptoms and signs of rheumatoid disease and, furthermore, that TNFalpha blockade protects joints from structural damage. Although these drugs are well tolerated and have a good overall safety profile, pitfalls to the use of anti-TNFalpha agents apparent with increasing clinical experience include rare cases of tuberculosis. The mechanism of action of anti-TNFalpha therapy is discussed. Clinical trials of interleukin-1 receptor antagonist show relatively modest anti-inflammatory efficacy and an effect on X-ray indicative of retardation of joint damage. Other pro-inflammatory cytokines representing potential therapeutic targets include interferon-beta, interferon-alpha, IL-6, IL-15, IL-17 and IL-18. I will consider preliminary data, where available, arising from clinical trials designed to inhibit the activity of such molecules. In this review I will also discuss the rationale and preliminary data for other potential therapeutic strategies designed to augment the activity of anti-inflammatory cytokines such as IL-4, IL-10, and IL-11 in rheumatoid disease.


Epigenetic Changes and Chromatin Reorganization in Brain Function: Lessons from Fear Memory Ensemble and Alzheimer's Disease.
Healthy brain functioning in mammals requires a continuous fine-tuning of gene expression. Accumulating evidence over the last three decades demonstrates that epigenetic mechanisms and dynamic changes in chromatin organization are critical components during the control of gene transcription in neural cells. Recent genome-wide analyses show that the regulation of brain genes requires the contribution of both promoter and long-distance enhancer elements, which must functionally interact with upregulated gene expression in response to physiological cues. Hence, a deep comprehension of the mechanisms mediating these enhancer-promoter interactions (EPIs) is critical if we are to understand the processes associated with learning, memory and recall. Moreover, the onset and progression of several neurodegenerative diseases and neurological alterations are found to be strongly associated with changes in the components that support and/or modulate the dynamics of these EPIs. Here, we overview relevant discoveries in the field supporting the role of the chromatin organization and of specific epigenetic mechanisms during the control of gene transcription in neural cells from healthy mice subjected to the fear conditioning paradigm, a relevant model to study memory ensemble. Additionally, special consideration is dedicated to revising recent results generated by investigators working with animal models and human postmortem brain tissue to address how changes in the epigenome and chromatin architecture contribute to transcriptional dysregulation in Alzheimer's disease, a widely studied neurodegenerative disease. We also discuss recent developments of potential new therapeutic strategies involving epigenetic editing and small chromatin-modifying molecules (or epidrugs).


What do we need to know to practice occupational therapy in the community?
One of the main challenges to occupational therapists in community practice is applying our existing knowledge base to support a different kind of practice in the community. This article explores the theory base in occupational therapy that informs three models of community practice: client-centered, community-based rehabilitation, and independent living. It defines these three preferred models of service delivery for community practice and looks at the knowledge requirements for each. Using a taxonomy developed to classify occupational therapy theory, the article examines existing theory and gaps in the theory base for occupational therapy in community practice. Finally, the article challenges practicing therapists, educators, and researchers to examine their use of theory and their underlying assumptions for meeting the challenge of community practice.


Real-time model learning using Incremental Sparse Spectrum Gaussian Process Regression.
Novel applications in unstructured and non-stationary human environments require robots that learn from experience and adapt autonomously to changing conditions. Predictive models therefore not only need to be accurate, but should also be updated incrementally in real-time and require minimal human intervention. Incremental Sparse Spectrum Gaussian Process Regression is an algorithm that is targeted specifically for use in this context. Rather than developing a novel algorithm from the ground up, the method is based on the thoroughly studied Gaussian Process Regression algorithm, therefore ensuring a solid theoretical foundation. Non-linearity and a bounded update complexity are achieved simultaneously by means of a finite dimensional random feature mapping that approximates a kernel function. As a result, the computational cost for each update remains constant over time. Finally, algorithmic simplicity and support for automated hyperparameter optimization ensures convenience when employed in practice. Empirical validation on a number of synthetic and real-life learning problems confirms that the performance of Incremental Sparse Spectrum Gaussian Process Regression is superior with respect to the popular Locally Weighted Projection Regression, while computational requirements are found to be significantly lower. The method is therefore particularly suited for learning with real-time constraints or when computational resources are limited.


Evaluation of abdominal exercises after stoma surgery: a descriptive study.
To evaluate the feasibility of exercises for the abdominal muscles in patients after colostomy or ileostomy formation on the following parameters: muscle activity, pain, discomfort, and difficulty of performing the exercises. Patients with a new stoma were divided into groups based on time after surgery: Early group, 0-2 weeks (n = 12); Intermediate group, 2-6 weeks (n = 15); and Late group, 6-12 weeks (n = 10). During a single individual test session, participants in each group performed a different set of 10-11 abdominal coordination and strengthening exercises for the abdominal muscles. Activity of the abdominal muscles was measured with electromyography. Pain, discomfort, and difficulty were rated for each exercise. For the Early group, muscle activity reaching a predetermined threshold was measured for half of the participants in a few exercises. In both the Intermediate group and the Late group, muscle activity reaching the onset criteria was measured for all muscles for a high percentage of participants in several exercises. Both strengthening and coordinating exercises were feasible based on low ratings of pain, discomfort, and difficulty. This study identified feasible exercises that activated the abdominal muscles at different time points after stoma formation. The observations can be used as guidance for the choice of exercises in clinical practice and future research.Implications for rehabilitationThe findings of this study can be used in clinical practice as guidance for choice of exercise at different time points after surgery.This study identified useful exercises for activating the abdominal muscles in rehabilitation after stoma surgery from two weeks on.In the first two postoperative weeks, there was limited involvement of the abdominal muscles with the evaluated exercises.Most of the evaluated abdominal exercises were feasible after stoma surgery based on pain, discomfort, and difficulty.


Lag Synchronization of Switched Neural Networks via Neural Activation Function and Applications in Image Encryption.
This paper investigates the problem of global exponential lag synchronization of a class of switched neural networks with time-varying delays via neural activation function and applications in image encryption. The controller is dependent on the output of the system in the case of packed circuits, since it is hard to measure the inner state of the circuits. Thus, it is critical to design the controller based on the neuron activation function. Comparing the results, in this paper, with the existing ones shows that we improve and generalize the results derived in the previous literature. Several examples are also given to illustrate the effectiveness and potential applications in image encryption.


Alburnus magnificus, a new species of bleak from the Orontes River drainage (Teleostei: Leuciscidae).
Alburnus magnificus, new species, is described from the northern Orontes River drainage in the eastern Mediterranean Sea basin. It is most similar and closely-related to A. qalilus from coastal rivers in Syria south of the Orontes. Alburnus magnificus is distinguished from A. qalilus by having the anal-fin origin below or behind the vertical through the last dorsal-fin ray, 4-5 scale rows between the lateral line and the anal-fin origin, and a flank pattern of bold black, grey or brown scales on a silvery or brown background. The two species are also distinguished by a minimum K2P distance of 1.8% in their COI sequence data.


Justicidin A-induced autophagy flux enhances apoptosis of human colorectal cancer cells via class III PI3K and Atg5 pathway.
Our previous reports showed that justicidin A (JA), a novel and pure arylnaphthalide lignan isolated from Justicia procumbens, induces apoptosis of human colorectal cancer cells and hepatocellular carcinoma cells, leading to the suppression of both tumor cell growth in NOD-SCID mice. Here, we reveal that JA induces autophagy in human colorectal cancer HT-29 cells by conversion of autophagic marker LC3-I to LC3-II. Furthermore, LC3 puncta and autophagic vesicle formation, and SQSTM1/p62 suppression were observed. Administration of autophagy inhibitor (bafilomycin A1 and chloroquine) and transfection of a tandem fluorescent-tagged LC3 (mRFP-GFP) reporter plasmid (ptfLC3) demonstrated that JA induces autophagy flux in HT-29 cells. Expression of LC3, SQSTM1, Beclin 1, and nuclear DNA double-strand breaks (representing apoptosis) were also detected in the tumor tissue of HT-29 cells transplanted into NOD-SCID mice orally administrated with JA. In addition, the expression of autophagy signaling pathway-related molecules p-PDK1, p-mTOR, p-p70S6k/p-RPS6KB2 was decreased, whereas that of class III PI3K, Beclin 1, Atg5-Atg12, and mitochondrial BNIP3 was increased in response to JA. Pre-treatment of the cells with class III PI3K inhibitor 3-methyladenine or Atg5 shRNA attenuated JA-induced LC3-II expression and LC3 puncta formation, indicating the involvement of class III PI3K and Atg5. A novel mechanism was demonstrated in the anticancer compound JA; pre-treatment with 3-methyladenine or Atg5 shRNA blocked JA-induced suppression in cell growth and colony formation, respectively, via inhibition of apoptosis. In contrast, administration of apoptosis inhibitor Z-VAD did not affect JA-induced autophagy. Our data suggest the chemotherapeutic potential of JA for treatment of human colorectal cancer.


Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment strategy for EGFR-mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFRT790M mutations in clinical trials. The effect of bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, combined with EGFR-TKIs has also been investigated. We hypothesized that the dose of afatinib and cetuximab could be reduced by combination with bevacizumab and that the triplet therapy may result in better tumor inhibition with tolerable toxicity. Using a xenograft mouse model with H1975-harboring EGFRL858R+T790M and RPC-9-harboring EGFR19DEL+T790M , we tested the efficacy of the triplet therapy with a modified dose of afatinib, cetuximab, and bevacizumab, and compared this therapy to single and double therapies. Triplet therapy with afatinib, cetuximab, and bevacizumab induced pathological complete remission in xenograft tumors with H1975 and RPC-9 cells versus tumors treated with single or double therapies. We saw no body weight loss in the mice. The triple therapy induced a significant reduction in CD31-positive vascular endothelial cells and increased cleaved caspase-3-positive cells in the tumors. This suggests that one mechanism underlying the deep remission could be suppression of neovascularization and induction of apoptosis by intensive inhibition of driver oncoproteins and VEGF. These results highlight the potential of afatinib, cetuximab, and bevacizumab to induce deep remission in tumors harboring EGFRT790M mutations. Therefore, clinical trials of this combination therapy are warranted.


How are granulocytes for transfusion best used? The past, the present and the future.
Granulocyte transfusions continue to be used in clinical practice, predominantly for treatment of refractory infection in the setting of severe neutropenia. There is biological plausibility for effectiveness in these patients with deficiencies of neutrophils, either as a consequence of disease or treatment. However, there is a chequered history of conducting and completing interventional trials to define optimal use, and many uncertainties remain regarding schedule and dose. Practice and clinical studies are severely limited by the short shelf life and viability of current products, which often restricts the timely access to granulocyte transfusions. In the future, methods are needed to optimise donor-derived granulocyte products. Options include use of manufactured neutrophils, expanded and engineered from stem cells. Further possibilities include manipulation of neutrophils to enhance their function and/or longevity. Granulocyte transfusions contain a heterogeneous mix of cells, and there is additional interest in how these transfusions may have immunomodulatory effects, including for potential uses as adjuncts for anti-cancer effects.


Multimodality Cardiac Imaging for the Assessment of Left Atrial Function and the Association With Atrial Arrhythmias.
Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the current moment. Numerous studies, however, have shown that functional measures may be superior to the maximal LA volume in several aspects and to possess clinical value even in the absence of structural abnormalities. Such functional measures could prove particularly useful in the setting of predicting atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing evidence has supported the use of functional measures and proven its superiority to the maximal LA volume, they have still not been adopted in clinical guidelines. The reason for this discrepancy may rely on the fact that there is little to no agreement on how to technically perform deformation analysis of the LA. Such technical considerations, limitations, and alternate imaging prospects will be addressed in this review.


A study on the prevalence of and risk factors for neck pain among university academic staff in Hong Kong.
The 1-year prevalence of neck pain and possible risk factors among university academic staff were investigated. Self-administered questionnaires were distributed to all the full-time academic staff in one of the universities in Hong Kong. The 1-year prevalence of neck pain was investigated. The relationship between individual factors, job nature, psychosocial factors, and neck pain were also analyzed. The 1-year prevalence of neck pain among after being an academic staff was 46.7%. A significant association was found between gender and neck pain (p = 0.02). The percentage of female academic staff with neck pain (62%) was higher than that in male staff (38%). This matched the results of other studies, which demonstrated that neck pain was more prevalent in women. There was a significant association between head posture during computer processing and neck pain (p = 0.02). Among those with neck pain during computer processing, 60.5% had a forward head posture. However, a low correlation between psychosocial factors and neck pain was demonstrated (r = 0.343). Academic staff in tertiary institutions could be considered as a high-risk group of job-related neck pain.


Evaluation of a structured preceptorship programme.
Preceptorship is a period in which newly qualified staff nurses receive support from an experienced nurse to smooth their transition into the service. District nurses (DNs) from the authors' trust informally expressed the need for a better transition between the completion of district nursing education and entry into the workforce. Hence, a structured preceptorship programme was developed and delivered. This article describes this service initiative and its evaluation by preceptors (n=14) and preceptees (newly qualified DNs; n=13). Both groups valued having a structured preceptorship programme. Preceptees agreed that having a named preceptor was very important, and preceptors felt that the role which they played was rewarding. Both groups felt that the role of the DN was a specialist role and that the preceptorship programme helped to support newly qualified staff make the transition into qualified DNs, clinical team leaders and, ultimately, caseload holders. A large-scale study of DN practice is required to develop a national consensus on the structure and content of preceptorship programmes for district nursing.


Foreground-Background Segmentation Revealed during Natural Image Viewing.
One of the major challenges in visual neuroscience is represented by foreground-background segmentation. Data from nonhuman primates show that segmentation leads to two distinct, but associated processes: the enhancement of neural activity during figure processing (i.e., foreground enhancement) and the suppression of background-related activity (i.e., background suppression). To study foreground-background segmentation in ecological conditions, we introduce a novel method based on parametric modulation of low-level image properties followed by application of simple computational image-processing models. By correlating the outcome of this procedure with human fMRI activity, measured during passive viewing of 334 natural images, we produced easily interpretable "correlation images" from visual populations. Results show evidence of foreground enhancement in all tested regions, from V1 to lateral occipital complex (LOC), while background suppression occurs in V4 and LOC only. Correlation images derived from V4 and LOC revealed a preserved spatial resolution of foreground textures, indicating a richer representation of the salient part of natural images, rather than a simplistic model of object shape. Our results indicate that scene segmentation occurs during natural viewing, even when individuals are not required to perform any particular task.


A versatile non-radioactive assay for DNA methyltransferase activity and DNA binding.
We present a simple, non-radioactive assay for DNA methyltransferase activity and DNA binding. As most proteins are studied as GFP fusions in living cells, we used a GFP binding nanobody coupled to agarose beads (GFP nanotrap) for rapid one-step purification. Immobilized GFP fusion proteins were subsequently incubated with different fluorescently labeled DNA substrates. The absolute amounts and molar ratios of GFP fusion proteins and bound DNA substrates were determined by fluorescence spectroscopy. In addition to specific DNA binding of GFP fusion proteins, the enzymatic activity of DNA methyltransferases can also be determined by using suicide DNA substrates. These substrates contain the mechanism-based inhibitor 5-aza-dC and lead to irreversible covalent complex formation. We obtained covalent complexes with mammalian DNA methyltransferase 1 (Dnmt1), which were resistant to competition with non-labeled canonical DNA substrates, allowing differentiation between methyltransferase activity and DNA binding. By comparison, the Dnmt1(C1229W) catalytic site mutant showed DNA-binding activity, but no irreversible covalent complex formation. With this assay, we could also confirm the preference of Dnmt1 for hemimethylated CpG sequences. The rapid optical read-out in a multi-well format and the possibility to test several different substrates in direct competition allow rapid characterization of sequence-specific binding and enzymatic activity.


Evanescent-absorption coefficient for diffuse source illumination: uniform- and tapered-fiber sensors.
A comparative study of evanescent-wave fiber-optic absorption sensors based on uniform and tapered fibers has been carried out. The expressions for an effective evanescent-absorption coefficient have been derived for diffused or Lambertian source illumination. It has been shown that the sensitivity of sensors depends on the numerical aperture of the fiber, the taper ratio, and the refractive index of the absorbing fluid. The higher the sensitivity the smaller the range of functional refractive indices of the fluid. In the case of taper, which fiber (with a low or high numerical aperture) has maximum sensitivity depends on the refractive index of the fluid.


Making sense of autism: Progressive engagement with science among parents of young, recently diagnosed autistic children.
This exploratory study examines the significance of science to parents whose children were recently diagnosed with an autism spectrum disorder. It asks: (I) In what manner did science emerge in parents' concerns and resources as they attempted to understand and advocate for their children? (2) Did some parents engage with science in a qualitatively deeper or more intense manner? Using longitudinal data from interviews and a novel data collection strategy called engagement mapping, it shows that parents asked questions and used resources that were strongly associated with science, but these were vastly outnumbered by "near-science" concerns and resources that mingled meanings from science and daily life. Several parents in the study wove together concerns and resources in an iterative pattern referred to here as progressive engagement with science.


Are you a cancer survivor? A review on cancer identity.
Individuals diagnosed with cancer have been shown to interpret the term "cancer survivor" differently and this may have implications for how they cope with their illness. This article reviews the empirical research conducted in the field and aims to formulate recommendations for future research. A literature search was conducted on PubMed, PsycInfo, Embase and CINAHL using search strategies customized for each database: standardized subject terms and a wide range of free-text terms for "cancer", "survivor", and "identity". Data from 23 eligible papers were extracted and summarized. Analysis of the studies revealed that individuals diagnosed with cancer could be categorized into five groups based on their attitudes towards being a cancer survivor: embracing, constructive, ambiguous, resisting and non-salient. Identification as "cancer survivor" was found to be highly prevalent within the breast cancer community (77.9 %) and least among individuals diagnosed with prostate cancer (30.6 %). Self-identifying as a cancer survivor was related to better quality of life and mental wellbeing, with those having a childhood diagnosis more likely to transition successfully into adult care. The findings show that, for a substantial group of individuals, "cancer survivor" is not a title earned upon receiving a cancer diagnosis or completion of treatment, but an identity that may be embraced in time after deliberation. Future studies should examine the endorsement rate in less common cancers and whether choice of cancer identity varies over time. Researchers and healthcare professionals should use caution when using the term "cancer survivor" so as not to alienate anyone who has been diagnosed with cancer but does not identify with it.


Granulocyte-macrophage colony-stimulating factor expression is regulated at transcriptional and posttranscriptional levels in a murine bone marrow stromal cell line.
We have reported modulation, by cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) and by hormonal cyclic-adenosine-monophosphate (cAMP) agonists, of hematopoietic growth factor production in the murine marrow adherent cell line +/+(-)1.LDA11. Previously, we reported that increased intracellular cAMP levels inhibited bioactive granulocyte-macrophage colony-stimulatory factor (GM-CSF) production stimulated by IL-1 or by the synergistic stimulus of IL-1 plus TNF-alpha. On the other hand, increased intracellular cAMP stimulated IL-6 synthesis in +/+(-)1.LDA11 cells. In addition, cAMP was additive with either IL-1 or IL-1 plus TNF-alpha in inducing production of soluble IL-6. In the present study, these observations were pursued mechanistically at the level of messenger RNA (mRNA) production. Northern blot analysis of steady-state mRNA for GM-CSF revealed induction by treatment of +/+(-)1.LDA11 cells with IL-1 or with TNF-alpha. The combined stimulation by IL-1 plus TNF-alpha resulted in supra-additive increases in GM-CSF expression by +/+(-)1.LDA11. Addition to stromal cells of the soluble cAMP agonist 8-bromo-cAMP (8BrcAMP) at 0.5 to 1 mM stimulated IL-6 mRNA expression acting alone, and it was additive with IL-1 or IL-1 plus TNF-alpha in stimulating IL-6 expression. On the other hand, 8BrcAMP inhibited GM-CSF mRNA expression stimulated by IL-1 or IL-1 plus TNF-alpha. Inhibition of GM-CSF mRNA by 8BrcAMP was time-dependent, starting 120 to 180 minutes posttreatment. In addition, inhibition of GM-CSF transcript expression in +/+(-)1.LDA11 by 8BrcAMP required the expression of a labile protein. Nuclear run-on assays revealed that GM-CSF and IL-6 genes were transcriptionally induced in +/+(-)1.LDA11 by incubation with IL-1 plus TNF-alpha. IL-6 transcription was further enhanced by 8BrcAMP co-incubation. More sensitive experiments using a luciferase reporter vector containing the GM-CSF promoter region were necessary to convincingly establish the role of TNF-alpha and 8BrcAMP on transcriptional induction of the GM-CSF gene in +/+(-)1.LDA11 stromal cells. Considering these results and an effect of 8BrcAMP on decreasing GM-CSF transcript stability in actinomycin-D (act-D) decay experiments, we conclude that the inhibitory effect of 8BrcAMP on GM-CSF expression is exerted at the posttranscriptional level. These data demonstrate that the intracellular level of cAMP has an important discriminatory role on expression of the cytokines GM-CSF and IL-6 in a model stromal cell line.


Biexciton emission and crystalline quality of ZnO nano-objects.
The design of cost-effective standards for the quality of nano-objects is currently a key issue toward their massive use for optoelectronic applications. The observation by photoluminescence of narrow excitonic and biexcitonic emission lines in semiconductor nanowires is usually accepted as evidence for high structural quality. Here, we perform time-resolved cathodoluminescence experiments on isolated ZnO nanobelts grown by chemical vapor deposition. We observe narrow emission lines at low temperature, together with a clear biexciton line. Still, drastic alterations in both the CL intensity and lifetime are observed locally along the nano-object. We attribute these to non-radiative recombinations at edge dislocations, closing basal plane stacking faults, inhomogeneously distributed along the NB length. This leads us to the conclusion that the observation of narrow excitonic and biexcitonic emission lines is far from sufficient to grade the quality of a nano-object.


Primary care professionals providing non-urgent care in hospital emergency departments.
In many countries emergency departments (EDs) are facing an increase in demand for services, long-waits and severe crowding. One response to mitigate overcrowding has been to provide primary care services alongside or within hospital EDs for patients with non-urgent problems. It is not known, however, how this impacts the quality of patient care, the utilisation of hospital resources, or if it is cost-effective. To assess the effects of locating primary care professionals in the hospital ED to provide care for patients with non-urgent health problems, compared with care provided by regular Emergency Physicians (EPs), We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialized register; Cochrane Central Register of Controlled Trials (The Cochrane library, 2011, Issue 4), MEDLINE (1950 to March 21 2012); EMBASE (1980 to April 28 2011); CINAHL (1980 to April 28 2011); PsychINFO (1967 to April 28 2011); Sociological Abstracts (1952 to April 28 2011); ASSIA (1987 to April 28 2011); SSSCI (1945 to April 28 2011); HMIC (1979 to April 28 2011), sources of unpublished literature, reference lists of included papers and relevant systematic reviews. We contacted experts in the field for any published or unpublished studies, and hand searched ED conference abstracts from the last three years. Randomised controlled trials, non-randomised studies, controlled before and after studies and interrupted time series studies that evaluated the effectiveness of introducing primary care professionals to hospital EDs to attend to non-urgent patients, as compared to the care provided by regular EPs. Two reviewers independently extracted data and assessed the risk of bias for each included study. We contacted authors of included studies to obtain additional data. Dichotomous outcomes are presented as risk ratios (RR) with 95% confidence intervals (CIs) and continuous outcomes are presented as mean differences (MD) with 95% CIs. Pooling was not possible due to heterogeneity. Three non randomised controlled studies involving a total of 11 203 patients, 16 General Practioners (GPs), and 52 EPs, were included. These studies evaluated the effects of introducing GPs to provide care to patients with non-urgent problems in the ED, as compared to EPs for outcomes such as resource use. The quality of evidence for all outcomes in this review was low, primarily due to the non-randomised design of included studies.The outcomes investigated were similar across studies; however there was high heterogeneity (I(2)>86%). Differences across studies included the triage system used, the level of expertise and experience of the medical practitioners and type of hospital (urban teaching, suburban community hospital).Two of the included studies report that GPs used significantly fewer healthcare resources than EPs, with fewer blood tests (RR 0.22; 95%CI: 0.14 to 0.33; N=4641; RR 0.35; 95%CI 0.29 to 0.42; N=4684), x-rays (RR 0.47; 95% CI 0.41 to 0.54; N=4641; RR 0.77 95% CI 0.72 to 0.83; N=4684), admissions to hospital (RR 0.33; 95% CI 0.19 to 0.58; N=4641; RR 0.45; 95% CI 0.36 to 0.56; N=4684) and referrals to specialists (RR 0.50; 95% CI 0.39 to 0.63; N=4641; RR 0.66; 95% CI 0.60 to 0.73; N=4684). One of the two studies reported no statistically significant difference in the number of prescriptions made by GPs compared with EPs, (RR 0.95 95% CI 0.88 to 1.03; N=4641), while the other showed that GPs prescribed significantly more medications than EPs (RR 1.45 95% CI 1.35 to 1.56; N=4684). The results from these two studies showed marginal cost savings from introducing GPs in hospital EDs.The third study (N=1878) failed to identify a significant difference in the number of blood tests ordered (RR 0.96; 95% CI 0.76 to 1.2), x-rays (RR 1.07; 95%CI 0.99 to 1.15), or admissions to hospital (RR 1.11; 95% CI 0.70 to 1.76), but reported a significantly greater number of referrals to specialists (RR 1.21; 95% CI 1.09 to 1.33) and prescriptions (RR 1.12; 95% CI 1.01 to 1.23) made by GPs as compared with EPs.No data were reported on patient wait-times, length of hospital stay, or patient outcomes, including adverse effects or mortality. Overall, the evidence from the three included studies is weak, as results are disparate and neither safety nor patient outcomes have been examined. There is insufficient evidence upon which to draw conclusions for practice or policy regarding the effectiveness and safety of care provided to non-urgent patients by GPs versus EPs in the ED to mitigate problems of overcrowding, wait-times and patient flow.


Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas.
Inactivation of the Transforming Growth Factor Beta (TGFbeta) tumor suppressor pathway contributes to the progression of Pancreatic Ductal AdenoCarcinoma (PDAC) since it is inactivated in virtually all cases of this malignancy. Genetic lesions inactivating this pathway contribute to pancreatic tumor progression in mouse models. Transcriptional Intermediary Factor 1 gamma (TIF1gamma) has recently been proposed to be involved in TGFbeta signaling, functioning as either a positive or negative regulator of the pathway. Here, we addressed the role of TIF1gamma in pancreatic carcinogenesis. Using conditional Tif1gamma knockout mice (Tif1gamma(lox/lox)), we selectively abrogated Tif1gamma expression in the pancreas of Pdx1-Cre;Tif1gamma(lox/lox) mice. We also generated Pdx1-Cre;LSL-Kras(G12D);Tif1gamma(lox/lox) mice to address the effect of Tif1gamma loss-of-function in precancerous lesions induced by oncogenic Kras(G12D). Finally, we analyzed TIF1gamma expression in human pancreatic tumors. In our mouse model, we showed that Tif1gamma was dispensable for normal pancreatic development but cooperated with Kras activation to induce pancreatic tumors reminiscent of human Intraductal Papillary Mucinous Neoplasms (IPMNs). Interestingly, these cystic lesions resemble those observed in Pdx1-Cre;LSL-Kras(G12D);Smad4(lox/lox) mice described by others. However, distinctive characteristics, such as the systematic presence of endocrine pseudo-islets within the papillary projections, suggest that SMAD4 and TIF1gamma don't have strictly redundant functions. Finally, we report that TIF1gamma expression is markedly down-regulated in human pancreatic tumors by quantitative RT-PCR and immunohistochemistry supporting the relevance of these findings to human malignancy. This study suggests that TIF1gamma is critical for tumor suppression in the pancreas, brings new insight into the genetics of pancreatic cancer, and constitutes a promising model to decipher the respective roles of SMAD4 and TIF1gamma in the multifaceted functions of TGFbeta in carcinogenesis and development.


Intranasal packs and haemostatic agents for the management of adult epistaxis: systematic review.
The mainstay of management of epistaxis refractory to first aid and cautery is intranasal packing. This review aimed to identify evidence surrounding nasal pack use. A systematic review of the literature was performed using standardised methodology. Twenty-seven eligible articles were identified relating to non-dissolvable packs and nine to dissolvable packs. Nasal packing appears to be more effective when applied by trained professionals. For non-dissolvable packs, the re-bleed rates for Rapid Rhino and Merocel were similar, but were higher with bismuth iodoform paraffin paste packing. Rapid Rhino packs were the most tolerated non-dissolvable packs. Evidence indicates that 96 per cent of re-bleeding occurs within the first 4 hours after nasal pack removal. Limited evidence suggests that dissolvable packs are effective and well tolerated by patients. There was a lack of evidence relating to: the duration of pack use, the economic effects of pack choice and the appropriate care setting for non-dissolvable packs. Rapid Rhino packs are the best tolerated, with efficacy equivalent to nasal tampons. FloSeal is easy to use, causes less discomfort and may be superior to Merocel in anterior epistaxis cases. There is no strong evidence to support prophylactic antibiotic use.


Using clinical journaling to capture critical thinking across the curriculum.
Clinical journaling is used as an integrated teaching methodology throughout the practicum component of a baccalaureate nursing curriculum. Two disciplines, Nursing and English, collaborated to develop clinical journaling guidelines to provide a consistent framework for student learning and evaluation in a variety of clinical settings. Students complete a weekly log for each clinical rotation. They identify learning goals, analyze events and relate them to nursing practice, use critical thinking to connect theory and practice, and reflect on the experience.A collegiate standard of writing is used. As the student advances through the program, a pattern of accomplishments and a cumulative integration of skills is evidenced to provide consistent standards for student evaluation.


Urinary bile acids as biomarkers for liver diseases I. Stability of the baseline profile in healthy subjects.
The role of bile acids (BAs) as biomarkers for liver injury has been proposed for decades. However, the large inter- and intra-individual variability of the BA profile has prevented its clinical application. To this end, we investigated the effect of covariates such as food, gender, age, BMI, and moderate alcohol consumption on the BA profile in healthy human subjects. The BA profile was characterized by the calculation of indices that describe the composition, sulfation, and amidation of total and individual BAs. Both inter- and intra-individual variabilities of BA indices were low in serum and even lower in urine compared with those of absolute concentrations of BAs. Serum BA concentrations increased with consumption of food, whereas urinary BA concentrations were mildly affected by food. Gender differences in the urinary and serum BA profile were minimal. The serum and urinary BA profiles were also not affected by age. BMI showed minimal effect on the urine and serum BA profile. Moderate alcohol consumption did not have a significant effect on the BA profile in both urine and serum. When the effect of the type of alcohol was studied, the results indicate that moderate drinking of beer does not affect BA concentrations and has minimal effect on BA indices, whereas moderate wine consumption slightly increases BA concentrations without affecting the BA indices. In summary, urinary BA indices showed lower variability and higher stability than absolute BA concentrations in serum and showed minimal changes to covariate effects suggesting their utility as biomarkers in clinic.


Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function.
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate homeostasis. Circulating FGF23 is elevated in chronic kidney disease (CKD) and independently associated with poor renal and cardiovascular outcomes and mortality. Because the study of FGF23 in individuals with normal renal function has received little attention, we examined in a large, population-based study of 1128 participants the associations of FGF23 with markers of mineral metabolism and renal function. The median estimated glomerular filtration rate (eGFR) of the cohort was 105 ml/min per 1.73 m(2), and the median plasma FGF23 was 78.5 RU/ml. FGF23 increased and plasma 1,25-dihydroxyvitamin D3 decreased significantly below an eGFR threshold of 102 and 99 ml/min per 1.73 m(2), respectively. In contrast, plasma parathyroid hormone increased continuously with decreasing eGFR and was first significantly elevated at an eGFR of 126 ml/min per 1.73 m(2). On multivariable analysis adjusting for sex, age, body mass index, and GFR, FGF23 was negatively associated with 1,25-dihydroxyvitamin D3, and urinary absolute and fractional calcium excretion but not with serum calcium or parathyroid hormone. We found a positive association of FGF23 with plasma phosphate, but no association with urinary absolute or fractional phosphate excretion and, unexpectedly, a positive association with tubular maximum phosphate reabsorption/GFR. Thus, in the absence of CKD, parathyroid hormone increases earlier than FGF23 when the eGFR decreases. The increase in FGF23 occurs at a higher eGFR threshold than previously reported and is closely associated with a decrease in 1,25-dihydroxyvitamin D3. We speculate that the main demonstrable effect of FGF23 in the setting of preserved renal function is suppression of 1,25-dihydroxyvitamin D3 rather than stimulation of renal phosphate excretion.


Emotional distress and quality of life in relatives of patients with severe brain injury: the first month after injury.
To investigate emotional distress and quality of life in a sample of Danish relatives of patients with severe brain injury at admission to intensive rehabilitation in the sub-acute phase. Clinical convenience sample. Participants included 31 primary relatives of patients with severe brain injury. The participants were recruited at admission to Traumatic Brain Injury Unit, Copenhagen University Hospital, Glostrup. All relatives completed the depression and anxiety scales from SCL-90-R (Symptom Checklist) and the Role Emotional, Social Function, Mental Health and Vitality scale of the SF-36 approximately 36 days after injury. Data concerning severity of injury, the patients' level of consciousness and function was also collected. The participants had significantly lower scores on all quality of life scales (p < 0.01) and significantly more symptoms of anxiety (p < 0.01) and depression (p < 0.01) than normal reference populations. Correlations were found between the patients' condition and the level of anxiety and depression in relatives. The majority of relatives had severely impaired quality of life and symptoms of anxiety and depression at the time of admission. Future research should focus on developing and evaluating interventions in the acute phase.


Errors in drug administration by anaesthetists in public hospitals in the Free State.
To investigate errors in administering drugs by anaesthetists working in public hospitals in the Free State province. Anonymous questionnaires were distributed to doctors performing anaesthesia in public hospitals in the Free State, i.e. 188 doctors at 22 public sector hospitals. Outcomes included demographic information on respondents, information regarding the administration of anaesthetics, reporting of errors, and the occurrence of errors during anaesthesia. The response rate was 46.3%; 48.8% were medical officers, and 39.3% of participants were involved in at least one event of erroneous drug administration. Registrars and specialists reported the most errors. Most events were of no clinical significance, caused no permanent harm to patients, and most commonly involved fentanyl and suxamethonium. Of the respondents, 23.8% indicated that they were aware of a South African standard for colour-coding syringe labels, and 92.9% indicated that they would report anaesthetic errors if a single reporting agency for such events existed. CONCLUSIONS. More than a third of participating anaesthetists were involved in a drug error at some stage in their practice. Preventive systems and precautionary measures should be put in place to reduce drug administration errors.


Folding analytical devices for electrochemical ELISA in hydrophobic R(H) paper.
This work describes a device for electrochemical enzyme-linked immunosorbent assay (ELISA) designed for low-resource settings and diagnostics at the point of care. The device is fabricated entirely in hydrophobic paper, produced by silanization of paper with decyl trichlorosilane, and comprises two zones separated by a central crease: an embossed microwell, on the surface of which the antigen or antibody immobilization and recognition events occur, and a detection zone where the electrodes are printed. The two zones are brought in contact by folding the device along this central crease; the analytical signal is recorded from the folded configuration. Two proof-of-concept applications, an electrochemical direct ELISA for the detection of rabbit IgG as a model antigen in buffer and an electrochemical sandwich ELISA for the detection of malarial histidine-rich protein from Plasmodium falciparum (Pf HRP2) in spiked human serum, show the versatility of this device. The limit of detection of the electrochemical sandwich ELISA for the quantification of Pf HRP2 in spiked human serum was 4 ng mL(-1) (10(2) pmol L(-1)), a value within the range of clinically relevant concentrations.


Metabolism of methanogens.
Methanogenic archaea convert a few simple compounds such as H2 + CO2, formate, methanol, methylamines, and acetate to methane. Methanogenesis from all these substrates requires a number of unique coenzymes, some of which are exclusively found in methanogens. H2-dependent CO2 reduction proceeds via carrier-bound C1 intermediates which become stepwise reduced to methane. Methane formation from methanol and methylamines involves the disproportionation of the methyl groups. Part of the methyl groups are oxidized to CO2, and the reducing equivalents thereby gained are subsequently used to reduce other methyl groups to methane. This process involves the same C1 intermediates that are formed during methanogenesis from CO2. Conversion of acetate to methane and carbon dioxide is preceded by its activation to acetyl-CoA. Cleavage of the latter compound yields a coenzyme-bound methyl moiety and an enzyme-bound carbonyl group. The reducing equivalents gained by oxidation of the carbonyl group to carbon dioxide are subsequently used to reduce the methyl moiety to methane. All these processes lead to the generation of transmembrane ion gradients which fuel ATP synthesis via one or two types of ATP synthases. The synthesis of cellular building blocks starts with the central anabolic intermediate acetyl-CoA which, in autotrophic methanogens, is synthesized from two molecules of CO2 in a linear pathway.


Telomerase Activity is Downregulated Early During Human Brain Development.
Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6-19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw.


The genetic outcomes of sex and recombination in long-term functionally parthenogenetic lineages of Australian Sitobion aphids.
The typical life cycle of an aphid is cyclical parthenogenesis which involves the alternation of sexual and asexual reproduction. However, aphid life cycles, even within a species, can encompass everything on a continuum from obligate sexuality, through facultative sexuality to obligate asexuality. Loss of the sexual cycle in aphids is frequently associated with the introduction of a new pest and can occur for a number of environmental and genetic reasons. Here we investigate loss of sexual function in Sitobion aphids in Australia. Specifically, we aimed to determine whether an absence of sexual reproduction in Australian Sitobion results from genetic loss of sexual function or environmental constraints in the introduced range. We addressed our aims by performing a series of breeding experiments. We found that some lineages have genetically lost sexual function while others retain sexual function and appear environmentally constrained to asexuality. Further, in our crosses, using autosomal and X-linked microsatellite markers, we identified processes deviating from normal Mendelian segregation. We observed strong deviations in X chromosome transmission through the sexual cycle. Additionally, when progeny genotypes were examined across multiple loci simultaneously we found that some multilocus genotypes are significantly over-represented in the sample and that levels of heterozygosity were much higher than expected at almost all loci. This study demonstrates that strong biases in the transmission of X chromosomes through the sexual cycle are likely to be widespread in aphids. The mechanisms underlying these patterns are not clear. We discuss several possible alternatives, including mutation accumulation during periods of functional asexuality and genetic imprinting.


A detailed phylogenetic analysis of FIV in the United States.
Feline immunodeficiency virus (FIV) is a lentivirus associated with AIDS-like illnesses in cats and has been used as a model for the study of human immunodeficiency virus (HIV). A feature of HIV and FIV infection is the continually increasing divergence among viral isolates between different individuals, as well as within the same individuals. The goal of this study was to determine the phylogenetic patterns of viral isolates obtained within the United States (U.S.) by focusing on the variable, V3-V4, region of the FIV envelope gene. Data indicate that FIV, from within the U.S., localize to four viral clades, A, B, C, and F. Also shown is the geographic isolation of strains where clade A and clade B are found predominately on the west coast; however, clade B is also found throughout the U.S. and represents the predominant clade. This study presents a complete and conclusive analysis of FIV isolates from within the U.S. and may be used as the essential basis for the development of an effective multi-clade vaccine.


Coincidence of obesity associated with cardio-renal abnormalities in Thais obese population.
To investigate the patterns and relationship among the metabolic syndrome (MS), coronary heart disease (CHD) and kidney function. A cross-sectional secondary data set of 9359 individuals, age 30-74 years, receiving annual health check-up in 2012 were used in this studied. Identification of MS and CHD development was determined by International Diabetes Federation criteria and Framingham risk score, respectively, while kidney function was assessed by using the estimate glomerulus filtration rate (eGFR) and chronic kidney disease epidemiology (CKD-EPI) formula. The prevalence of MS was 16.1%. The majority pattern of MS in male displayed abnormalities of body mass index (BMI) plus triglyceride and blood pressure (BP). Most of them had high risk of CHD, and kidney function in stage 1 and 2. Furthermore, abnormalities of BMI plus BP and blood glucose were the main components related to high risk of CHD, and stage 1 of kidney function in female. This finding showed the cleared pattern of the sequential abnormality factors which potentially use for setting the activity and empowerment team to prevention, promotion, and treatment strategy in MS patients. Particularly, BMI is the first assessment and then follow by blood pressure and blood sugar which could be used as the guideline for reducing MS associated with CHD and kidney disorder in Thai population.


Health insurance literacy and health service utilization among college students.
Objective: Health literacy and health insurance literacy affect healthcare utilization. The purpose of this study was to determine the relation between health insurance knowledge, self-efficacy, and student healthcare utilization in the past year. Participants: A random sample of 1,450 respondents, over the age of 18, attending a public university in the southeastern United States completed a survey in March 2017. Methods: A model was constructed to test the effect of health insurance self-efficacy on the relation between knowledge and healthcare utilization in the past year. Results: Health insurance knowledge (M = 5.8, range 0-10) and self-efficacy (M = 2.48, range 1-4) were low. Self-efficacy was a significant moderator when explaining healthcare utilization in the past year. Conclusions: College students have low knowledge and self-efficacy regarding health insurance. These findings can be used for developing policies and self-efficacy-based health education programs that may increase student healthcare utilization.


Information-driven search strategies in the board game of CLUE.
This paper presents an information-driven sensor management problem, referred to as treasure hunt, which is relevant to mobile-sensor applications such as mine hunting, monitoring, and surveillance. The objective is to infer a hidden variable or treasure by selecting a sequence of measurements associated with multiple fixed targets distributed in the sensor workspace. The workspace is represented by a connectivity graph, where each node represents a possible sensor deployment, and the arcs represent possible sensor movements. An additive conditional entropy reduction function is presented to efficiently compute the expected benefit of a measurement sequence over time. Then, the optimal treasure hunt strategy is determined by a novel label-correcting algorithm operating on the connectivity graph. The methodology is illustrated through the board game of CLUE, which is shown to be a benchmark example of the treasure hunt problem. The game results show that a computer player implementing the strategies developed in this paper outperforms players implementing Bayesian networks, Q-learning, or constraint satisfaction, as well as human players.


A combination of six psychoactive pharmaceuticals at environmental concentrations alter the locomotory behavior of clonal marbled crayfish.
Pharmaceutically active compounds (PhACs) are ubiquitous in the aquatic environment worldwide and considered emerging contaminants. Their effects on growth, behavior, and physiological processes of aquatic organisms have been identified even at very low concentrations. Ecotoxicological investigations have primarily focused on single compound exposure, generally at a range of concentrations. In the natural environment, pollutants seldom occur in isolation, but little is known about the effects and risks of combinations of chemicals. This study aimed to investigate the effects of concurrent exposure to six psychoactive PhACs on locomotory behavior and life history traits of clonal marbled crayfish Procambarus virginalis. Crayfish were exposed to ~1 μg L-1 of the antidepressants sertraline, citalopram, and venlafaxine; the anxiolytic oxazepam; the opioid tramadol; and the widely abused psychostimulant methamphetamine. In the absence of shelter, exposed crayfish moved significantly shorter distances and at lower velocity and showed significantly less activity than controls. With available shelter, exposed crayfish moved significantly more distance, showed higher activity, and spent a significantly more time outside the shelter than controls. Molting, mortality, and spawning frequency did not vary significantly between the groups. Hemolymph glucose level did not vary among groups and was not correlated with observed behaviors. Results suggest that environmental concentrations of the tested compounds in combination can alter the behavior of non-target aquatic organisms as individual exposure of these compounds, which may lead to disruption of ecosystem processes due to their reduced caution in polluted conditions. Further research is needed using varied chemical mixtures, exposure systems, and habitats, considering molecular and physiological processes connected to behavior alterations.